Prilocaine and hydrofluourocarbon aerosol preparations

ABSTRACT

Aerosol compositions used for anesthetizing mammals in both human and veterinary applications include prilocaine base solubilized in the hydrofluorocarbon (HFC) propellants 1,1,1,2-tetrafluoroethane and 1,1,1,2,3,3,3-heptafluoropropane. Prilocaine base has been found to be readily soluble in HFC propellants when combined in liquid or micro rod form, and a solution stable to temperatures as low as -82° C. is formed upon combination of the two components. In the aerosol compositions, the HFCs are the only propellants used. Additional pharmaceutical constituents can also be combined the the prilocaine base/HFC composition to provide a multi-component anesthetic, and it has been found that the presence of prilocaine in the combination can assist in solubilizing and/or suspending these pharmaceutical consituents. Some example pharmaceutical compositions within the practice of this invention include HFC, prilocaine base, and a pharmaceutical other prilocaine selected from the group consisting of bronchodilators, antiinflammatories, antitusives, vasoactive drugs, vasoconstrictors, antibiotics, peptides, steroids, enzymes, antihistamines, hormones, enzyme and receptor inhibitors and agonists, 5-aminolevulinic acid, antiseptics, disinfectants, procaine, cocaine, chloroprocaine, tetractaine, mepivacaine, lidocaine, bupivacaine, etidocaine, ropivacaine, benzocaine, and phenylephrine.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of the co-pendingpatent application filed Mar. 24, 1995, having U.S. Ser. No. 08/408,877,and the patent application filed May 2, 1994, having U.S. Ser. No.08/236,408, now U.S. Pat. No. 5,453,445, and the co-pending patentapplication filed Mar. 17, 1995, having U.S. Ser. No. 08/405,930, andthe complete contents of these three patent applications are hereinincorporated by reference.

DESCRIPTION BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention is generally related to aerosol formulations which includehydrofluoride propellants and prilocaine base.

2. Description of the Prior Art

Prilocaine is a local anesthetic drug which has the chemical formula:##STR1## Prilocaine is described in British Patent 839,943 (1960 toAstra), and takes the form of crystalline needles having a melting pointof 37°-38° C. The hydrochloride salt, having the formula C₁₃ H₂₁ ClN₂ O,is crystallized from ethanol and isopropyl ether, and is readily solublein water.

Local anesthetic drugs block nerve impulses by interfering with theopening of voltage gated sodium channels of excitable membranes, such asneuronal cell membranes. When enough channels are blocked, neuronalconduction is terminated within the anesthetized portion of theparticular nerve axon. This mechanism of pain relief is quite differentfrom those used by analgesic agents.

The potency of anesthetics in clinical situations depends on both theability to reach the nerve fibers and their intrinsic blockingactivities. Factors such as nerve sheath penetration, vascularabsorption, and local tissue binding are all important determinants offunctional potency. In addition, volume, pH, and buffering capacity ofthe injected anesthetic solution are important.

Local anesthetics are traditionally injected into the desired site ofaction by the use of a needle and syringe. Most formulations of localanesthetics are aqueous solutions of the hydrochloride salt forms of thedrug in 0.5-2% weight/volume concentrations. These solutions aredesigned for injection either diffusely into tissue, around nerves, orinto the intrathecal or epidural spaces.

The delivery of local anesthetic agents to skin wounds remains a problemand is largely still achieved by injection of the aqueous localanesthetic around or into the wound. This treatment mechanism can bedisadvantageous because the needle itself causes pain on penetration,and, the volume of anesthetic solution can cause stretching at the site,which also causes pain. Furthermore, preservatives such as parabens,ethyl alcohol, cetylpyridinium chloride, benzalkonium chloride, and thelike, which may be used in the aqueous solution can cause stinging atthe wound site.

A topical formulation of 0.5% tetracaine hydrochloride, epinephrine1:2000, and 11.8% cocaine hydrocloride, is described in Handbook ofPediatric Emergencies, 1994, Ed. Baldwin, Little, Brown and Company.This formulation is applied by holding a cotton ball soaked in thesolution for a period of 10-15 minutes. This treatment scheme andformulation suffers from the slow absorption of the salt form of thelocal anesthetic which requires that the solution be held in place forlong periods of time, the use of cotton balls directly on the woundsite, and the requirement of cleaning the wound prior to application ofthe formulation. In addition, in order to obtain deep blocking, thetreatment scheme must be supplemented with injection of a localanesthetic formulation.

Topical anesthesia requires rapid absorption of drug in order to blocknerve conduction. Topically applied gels and fluids have not provensuccessful in many environments. For example, intraurethrally deliveredlidocaine gel was shown to be no more effective than plain lubricantjelly during cystoscopy (see, Stein et al., Journal of Urology, June1994, Vol. 151, pages 1518-1521).

Lidocaine has been delivered in aerosol form to the mucous membranes ofthe airway using nebulized aqueous preparations of the lidocainehydrochloride salt and using metered dose inhaler (MDI) formulationswith chlorofiuorocarbon (CFC) propellants and solubilizing and/ordispersing agents. However, experience has shown that these formulationssuffer from large droplet formation which prevents satisfactoryinhalable or indirect delivery to the upper airway, including the larynxand trachea. In addition, the requirement of organic solvents andadjuvants in the aerosol formulations limits the concentration of theactive medicament, and thus limits the dispensable dose. Moreover, theseformulations have not been used topically and would not be successful intopical application because the adjuvants and solvents are themselvesirritants which would cause pain when administered to sensitive mucousmembranes and wounds.

Chlorofiuorocarbon (CFC) propellants have been widely used in aerosolformulations; however, CFC propellants are being phased out underinternational treaties due to their possible adverse impact on the ozonelayer. Hydrofluorocarbon (HFC) propellants have been investigatedextensively as substitutes for CFCs. While chemically similar to toCFCs, HFCs have some property differences that have made formulatingcertain products very difficult, and particularly formulating medicaland pharmaceutical aerosols wherein the ability to provide a controlledamount of drug and, in some instances, particles or droplets ofrespirable size (e.g., less than 10 μm), is extremely important.

SUMMARY OF THE INVENTION

An object of this invention is to provide novel aerosol formulationswhich include prilocaine, with or without additional medicaments, in HFCpropellants, without additional organic solvents and surfactants.

Another object of this invention is to provide a method of usingprilocaine as a solubilizing agent in HFC propellants.

Another object of this invention is to provide a new composition ofprilocaine wherein prilocaine, in liquid or amorphous form, isassociated with an HFC propellant.

According to the invention, prilocaine in base form has been found to besoluble in the HFC propellants 1,1,1,2-tetrafluoroethane and1,1,1,2,3,3,3-heptafluoropropane. Prilocaine is soluble when combinedwith the HFC propellant in liquid form, but is not soluble when combinedwith the HFC propellant in its crystalline form. The combination ofprilocaine base in liquid form and HFC propellant forms a stable liquidsolution having an oily consistency. When prilocaine base in liquid formis mixed with the HFC propellant it is thought to form a 1:1 molecularionic complex that keeps the prilocaine in solution and alters thesolubility of this complexed mixture such that it is completely miscibleor soluble in prilocaine. The prilocaine complexed HFC propellant hasaltered physical characteristics with improved solubility, improvedsuspension characteristics, a low vapor pressure and higher viscosity.The association or complex between prilocaine and HFC propellants isdisrupted by the presence of water or ethanol resulting in the releaseof the HFC propellant. Prilocaine liquid can be combined with othermedicaments, and particularly other anesthetics, and serve as asolubilizing agent by improving the solubility characteristics of theHFC propellant such that the added local anesthetic forms a stablesolution in the prilocaine/HFC solution complex. The oily character ofthe prilocaine liquid/HFC complex may serve as a valve lubricating aidwhen dispensing the aerosol formulation from an MDI; thereby, overcomingor obviating the conventional formulations which need additional valvelubricants. The prilocaine liquid/HFC complex also allows the creationof stable suspensions of certain particulate medicaments (e.g.,beta-agonists such as albuterol, etc.). The liquid character of theprilocaine/HFC complex may be advantageous in topical treatmentmethodologies since the prilocaine can be sprayed onto a site to coatthe site with a liquid, as opposed to a fine powder, which will be morerapidly absorbed due to the liquid character of the prilocaine, the factthat the prilocaine is present as a lipid-soluble base, and the rapiddeparture of the complexed HFC propellant from the interaction of thecomplex with water on the membrane and skin surfaces of the patient.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

Liquid prilocaine base can be made by suspending prilocainehydrochloride in ethyl acetate and washing with a suitable aqueous base,such as sodium bicarbonate, until all the solid is consumed. The ethylacetate can be removed using standard rotary evaporation or otherprocedures. After removal of ethyl acetate, the prilocaine base residueis then dissolved in a lower boiling point solvent, such asdichloromethane, to remove the ethyl acetate by azeotropic distillation.The dichloromethane is then evaporated off using a rotary evaporator,and the prilocaine base is dried under high vacuum.

The prilocaine base obtained by the above procedure was a liquid at roomtemperature, but was easily converted to its usual crystalline needleform by cooling or by the addition of crystal seeds to the liquid. Asnoted above, prilocaine is ordinarily a solid at room temperature whichhas the form of crystalline needles that melt at 38° C. However, theprocessing conditions used formed a liquid prilocaine base below itsnormal melting point. This is not an unusual occurrence where a lowmelting point solid is found to remain in liquid form below its meltingpoint; however, this property in prilocaine base has been heretoforunknown. Further cooling or the addition of crystal seeds crystallizesthese substances and they remain in solid form up to their predictedmelting point.

A reference standard prilocaine base sample obtained from the AstraPharmaceutical Company of Sweden was used to verify the nature andpurity of the liquid prilocaine base as described above. It wasconfirmed using thin layer chromatography on silica gel, infra-red (IR)spectrometry, and nuclear magnetic resonance (NMR) imaging that theliquid prilocaine base was the same as the standard prilocaine base.

It has been discovered that the liquid prilocaine base can be readilysolubilized or absorbed into HFC propellants 1,1,1,2-tetrafiuoroethaneand 1,1,1,2,3,3,3-heptafluoropropane. The combination of liquidprilocaine base and the HFC propellant forms a stable oily liquid.

By contrast, prilocaine base in its ordinary crystalline needle form isnot soluble in HFC propellants. The crystal structure is thought toprevent the polar/ionic interaction of prilocaine and HFC propellant andthe crystals remain insoluble.

When the crystalline needles are melted by heating to a temperatureabove 38° C., the liquid was found to be readily solubilized andabsorbed in the HFC propellants to form a stable oily liquid. As long asno needle crystals are present, the prilocaine base/HFC combinationremains stable when cooled down to -82° C.; however, seeding thesolution with needles will cause dissolution of the prilocaine base/HFCcombination.

In addition to liquid prilocaine base being found to be soluble in HFCs,it has been found that prilocedne base in micro rod crystal form, asopposed to the usual needle form, is soluble in HFC propellants. Microrods of prilocaine base may be obtained using precipitation andfiltering from a super-saturated solution. The Reference Standard Sampleof prilocaine base from Astra Pharmaceuticals was provided in micro rodcrystal form. The micro rods are identical to the crystalline needles ofprilocaine base chemically, but not physically.

An important feature of this invention is that prilocaine base be usedin liquid form or micro-rod form when making aerosol formulations withHFC propellants. Combining liquid or micro-rod prilocaine base with HFCpropellants produces a stable complex or association that has the formof an oily liquid solution which can be used in MDIs or otherformulations. The solution is ideal for topical delivery to a wound siteor the like, in that the prilocaine base is applied as a liquid and isabsorbed quickly, absorption is enhanced by the prilocaine being presentin its lipid soluble base form, and the complexed HFC propellant quicklydissociates from the prilocaine upon contact with water and othercontaminants at the site. The rapid absorption allows for quick andeffective local anesthesia without causing pain or discomfort onapplication. Because the prilocaine base is in liquid form as it issprayed, it has the utility of forming a thin film coating on any siteneeding to be anesthetized. Such sites include the mucous membranes ofthe airway, gastrointestinal tract and genito-urinary tract, and allwound surfaces where the epidermis is comprimised to allow rapidabsorption of topical local anesthetic as well as internal organsurfaces exposed during surgical procedures. The oily character of theliquid improves asorption to the applied surface while remaining easy towash or wipe off.

Example 1 describes the formation of the complex of liquid prilocainebase and HFC propellants.

EXAMPLE 1

Liquid prilocaine base, provided as an oily liquid without any crystalseeds, is readily miscible with the hydrofluorocarbon propellants1,1,1,2-tetrafiuoroethane (HFC-134a) and1,1,1,2,3,3,3-heptafluoropropane (HFC-227). Likewise, prilocaine base inmicro rod crystalline form is readily miscible with thehydrofluorocarbon propellants 1,1,1,2-tetrafiuoroethane (HFC-134a) and1,1,1,2,3,3,3-heptafluoropropane (HFC-227). The combination of theliquid prilocaine base or micro rod prilocaine base and the HFCpropellants forms a stable liquid solution.

During formulation of a particular prilocaine base/HFC solution, liquidprilocaine was placed in a 4 ounce glass bottle of known weight. Thebottle was weighed to determine the weight of liquid prilocaine base.The bottle was then sealed with a continuous valve. HFC-134a was addedto the bottle by pressure fill. The bottle was weighed again todetermine the weight of HFC-134a added. The bottle was agitated gentlyto ensure intermingling of the liquid prilocaine base and the HFC. Themixture was found to form a clear and stable solution that did notprecipitate out the prilocaine base when left standing or cooled. Thevalve was opened for short intervals to let out vaporized HFC-134a gas,and the bottle was weighed intermittently. The solution remained clearand stable after each portion of HFC-134a gas was discharged. Thisprocess was continued until all vaporizable gas was let out of thebottle. The weight of the bottle after the vaporizable gas had beendischarged indicated a 1:1 weight ratio of prilocaine:HFC-134a residue(product remaining in bottle). By leaving the bottle open fortwenty-four hours with intermittent weighing, it was determined that theHFC-134a slowly came out of solution until the weight of the bottleindicated the presence of liquid prilocaine base alone. Infra-redspectroscopy confirmed that the recovered liquid prilocaine base wasunaltered by the interaction with HFC-134a.

Cooling of a 1:1 mixture of prilocaine:HFC-134a prepared as describedabove to -82° C. did not result in prilocaine crystallizing out ofsolution. Instead, the prilocaine:HFC-134a formed a more viscoussolution. This result is surprising in view of prilocaine oridinarilyhaving a 38° C. melting point, and the 1:1 solution being highlyconcentrated, and it further suggests that some form of association orcomplex (e.g., ionic) between liquid prilocaine base and the HFC iscreated. Upon rewarming of the viscous oil to room temperature, theprilocaine:HFC-134a remained a liquid. The cooling test described abovedemonstrates that the liquid prilocaine base can be used in cold-fillingoperations that are ordinarily used in MDI packaging or the like withoutadverse consequences.

Seeding of the 1:1 solution with prilocaine base needle crystalsresulted in the prilocaine base crystallizing out of solution overseveral days.

The association of liquid prilocaine base with HFC propellants has beenfound to allow its use as a solubilizing agent for dissolving and/ordispersing other medicaments within HFC propellants. In particular,prilocaine base can be used as a solubilizing aid for other localanesthetics, most of which are not ordinarily soluble in HFCpropellants. For example, prilocaine base can be used in HFC propellantsin combination with the anesthetics procaine, cocaine, chloroprocaine,tetracaine, mepivacaine, lidocaine, bupivacaine, etidiocaine,ropivacaine, and benzocaine. Prilocaine may be used in the preparationof HFC aerosol formulations that are used in inhalation (nasal and/ororal), and topical delivery (e.g., skin wounds, hollow viscus and bodycavity delivery), and may be used to solubilize, disperse and/or formstable suspensions with other medicaments including, for example,bronchodilators, anti-inflammatories, antitussives, vasoactive drugs,vasoconstrictors, antibiotics, peptides, steroids, enzymes,antihistamines, benzodiazepines, anti-psychotics, sedatives, vitamins,hormones, enzyme and receptor inhibitors and agonists, 5-aminolevulinicacid and similar agents, antiseptics and disinfectants, etc.

Example 2 provides the compositions of several different HFC aerosolformulations which have been prepared. It can be seen that prilocainebase can be used at widely varying concentrations and may range from1-99% by weight of the aerosol formulation. Most preferably, the liquidprilocaine base will constitute 1-60% by weight of the HFC aerosolformulation. The HFC propellant can constitute 1-99% by weight of theaerosol formulation, and most preferably 60% to 95% by weight of theaerosol formulation.

If an additional medicament is combined with prilocaine and the HFCpropellant, it can constitute 0.01-99% by weight of the aerosolformulation, and most preferably 0.01 to 10% by weight of the aerosolformulation.

EXAMPLE 2

Using the same general method of Example 1, the following formulationswere prepared and they provided stable solutions.

    ______________________________________                                        Formulation 1                                                                 Prilocaine base                                                                              140    mg       4.4%  w/w                                      Lidocaine base 1260   mg       40.0% w/w                                      HFC-134a       1760   mg       55.6% w/w                                      Formulation 2                                                                 Prilocaine base                                                                              340    mg       15.5% w/w                                      Lidocaine base 1260   mg       57.7% w/w                                      HFC-134a       580    mg       26.6% w/w                                      Formulation 3                                                                 Prilocaine base                                                                              520    mg       34.9% w/w                                      Lidocaine base 1260   mg       84.7% w/w                                      HFC-134a       175    mg       11.7% w/w                                      Formulation 4                                                                 Prilocaine base                                                                              411    mg       33.4% w/w                                      Lidocaine base 476    mg       38.6% w/w                                      HFC-134a       344    mg       28.0% w/w                                      ______________________________________                                    

When cooled to -82° C., formulations 1-4 experienced crystalprecipitation of the lidocaine base leaving a thick oily solution ofprilocaine and HFC-134a. The lidocaine crystals went back into solutionupon rewarming. When the bottle was left open for longer than 24 hours,the HFC-134a evaporated and the local anesthetics crystallized whencooled.

    ______________________________________                                        Formulation 5                                                                 Benzocaine base                                                                              322     mg      3.7%  w/w                                      HFC-134a       8283    mg      no solution                                    Formulation 6                                                                 Prilocaine base                                                                              184.6   mg      56.2% w/w                                      Benzocaine base                                                                              12.7    mg      3.8%  w/w                                      HFC-134a       131.2   mg      40.0% w/w                                                           clear solution                                           Formulation 7                                                                 Bupivacaine base                                                                             30.0    mg      0.3%  w/w                                      HFC-134a       10000   mg      no solution                                    Formulation 8                                                                 Bupivacaine base                                                                             166.0   mg      33.5% w/w                                      Prilocaine base                                                                              176.0   mg      35.5% w/w                                      HFC-134a       153.0   mg      31.0% w/w                                                           clear solution                                           ______________________________________                                    

Formulations 4-8 show that ordinarily insoluble anesthetics (e.g.,benzocaine and bupivacaine) can be solubilized in HFC propellants whenthe liquid prilocaine base:HFC-134a solution is used. When cooled to-82° C., the benzocaine and bupivacaine precipitated out of solution.Upon rewarming, the benzocaine and bupivacaine dissolved back intosolution.

    ______________________________________                                        Formulation 9                                                                 Tetracaine base                                                                              60     mg       1.9%  w/w                                      HFC-134a       3000   mg       98.1% w/w                                                           clear solution                                                     maximum solubility of tetracaine                                    Formulation 10                                                                Tetracaine base                                                                              150    mg       5.8%  w/w                                      Prilocaine base                                                                              178    mg       6.9%  w/w                                      HFC-134a       2250   mg       87.3% w/w                                      ______________________________________                                    

Formulations 9-10 demonstrate that prilocaine can be used to enhance thesolubility of certain medicaments in HFC propellants

    ______________________________________                                        Formulation 11                                                                Phenylephrine base                                                                            6      mg       0.12% w/w                                     HFC-134a        4890   mg       no solution                                   Formulation 12                                                                Phenylephrine base                                                                            8      mg       0.2%  w/w                                     Prilocaine base 993    mg       24.7% w/w                                     Lidocaine base  1009   mg       25.1% w/w                                     HFC-134a        1110   mg       50.0% w/w                                     ______________________________________                                    

The three medicament bases were first heated and dissolved together.This formulation produced a stable suspension of the phenylephrine. Nosigns of crystal growth were observed.

    ______________________________________                                        Formulation 13                                                                Phenylephrine base                                                                             3      mg      0.2%  w/w                                     Prilocaine base  402    mg      24.7% w/w                                     Bupivacaine base 409    mg      25.1% w/w                                     HFC-134a         814    mg      50.0% w/w                                     ______________________________________                                    

This formulation resulted in a stable suspension. Preheating and mixingof the base compounds was not required in this formulation but isrecommended as a method of obtaining even particle sizes ofphenylephrine in the suspension.

Formulations 11-13 demonstrate the utility of prilocaine in acting as adispersing agent (as opposed to solubilizing agent) in forming a stablesuspension of a medicament.

While the invention has been described in terms of its preferredembodiments, those skilled in the art will recognize that the inventioncan be practiced with modification within the spirit and scope of theappended claims.

We claim:
 1. An aerosol composition for delivering topical localanesthetic to a mammal, comprising:1-99% wt of hydrofluorocarbonpropellant selected from the group consisting of1,1,1,2-tetrafluoroethane and 1,1,1,2,3,3,3-heptafluoropropane andcombinations thereof, said hydrofluorocarbon propellant being the solepropellant in said aerosol composition; 1-99% wt prilocaine basesolubilized within said hydrofluorocarbon propellant, said prilocainebase and said hydrofluorocarbon propellant forming a solution that isstable at reduced temperature of at least -82° C.; and 0.01-99% wt of apharmaceutical other than prilocaine solubilized in saidhydrofluorocarbon propellant selected from the group consisting ofbronchodilators, antiinflammatories, antitusives, vasoactive drugs,vasoconstrictors, antibiotics which are not antiseptics, peptides whichare not enzymes, steroids, enzymes, antihistamines, hormones,5-aminolevulinic acid, antiseptics, disinfectants, procaine, cocaine,chloroprocaine, tetracaine, mepivacaine, lidocaine, bupivacaine,etidocaine, ropivacaine, benzocaine, and phenylephrine.
 2. An aerosolcomposition for delivering topical local anesthetic to a mammal,comprising:1-99% wt of hydrofluorocarbon propellant selected from thegroup consisting of 1,1,1,2-tetrafluoroethane and1,1,1,2,3,3,3-heptafluoropropane and combinations thereof, saidhydrofluorocarbon propellant being the sole propellant in said aerosolcomposition; 1-99% wt prilocaine base solubilized within saidhydrofluorocarbon propellant, said prilocaine base and saidhydrofluorocarbon propellant forming a solution that is stable atreduced temperature of at least -82° C.
 3. A method of solubilizing orsuspending medicaments in hydrofluorocarbon propellants to form anaerosol composition for delivery to a mammal, comprising the stepsof:dissolving 1-99 wt % prilocaine base in 1-99% wt of ahydrofluorocarbon propellant selected from the group consisting of1,1,1,2-tetrafluoroethane and 1,1,1,2,3,3,3-heptafluoropropane, andcombinations thereof, to produce a solution of prilocaine base andhydrofluorocarbon propellant that is stable at a reduced temperature ofat least -82° C., said hydrofluorocarbon propellant being the solepropellant in said aerosol composition; and incorporating 0.01-99wt % ofa medicament other than prilocaine selected from the group consisting ofbronchodilators, antiinflammatories, antitusives, vasoactive drugs,vasoconstrictors, antibiotics which are not antiseptics, peptides whichare not enzymes, steroids, enzymes, antihistamines, hormones,5-aminolevulinic acid, antiseptics, disinfectants, procaine, cocaine,chloroprocaine, tetracaine, mepivacaine, lidocaine, bupivacaine,etidocaine, ropivacaine, benzocaine, and phenylephrine into saidsolution by a method selected from the group consisting of solubilizingand suspending.
 4. The method of claim 3 wherein said dissolving andincorporating steps are performed simultaneously.
 5. The aerosolcomposition of claim 1 wherein said pharmaceutical is a bronchodilator.6. The aerosol composition of claim 1 wherein said pharmaceutical is anantiinflammatory.
 7. The aerosol composition of claim 1 wherein saidpharmaceutical is an antitusive.
 8. The aerosol composition of claim 1wherein said pharmaceutical is selected from the group consisting ofvasoactive drugs and vasoconstrictors.
 9. The aerosol composition ofclaim 1 wherein said pharmaceutical is an antibiotic.
 10. The aerosolcomposition of claim 1 wherein said pharmaceutical is a peptide.
 11. Theaerosol composition of claim 1 wherein said pharmaceutical is a steroid.12. The aerosol composition of claim 1 wherein said pharmaceutical is anenzyme.
 13. The aerosol composition of claim 1 wherein saidpharmaceutical is an antihistamine.
 14. The aerosol composition of claim1 wherein said pharmaceutical is a hormone.
 15. The aerosol compositionof claim 1 wherein said pharmaceutical is selected from the groupconsisting of enzyme and receptor inhibitors and agonists.
 16. Theaerosol composition of claim 1 wherein said pharmaceutical is5-aminolevulinic acid.
 17. The aerosol composition of claim 1 whereinsaid pharmaceutical is an antiseptic.
 18. The aerosol composition ofclaim 1 wherein said pharmaceutical is a disinfectant.
 19. The aerosolcomposition of claim 1 wherein said pharmaceutical is procaine.
 20. Theaerosol composition of claim 1 wherein said pharmaceutical is cocaine.21. The aerosol composition of claim 1 wherein said pharmaceutical ischloroprocaine.
 22. The aerosol composition of claim 1 wherein saidpharmaceutical is tetracaine.
 23. The aerosol composition of claim 1wherein said pharmaceutical is mepivacaine.
 24. The aerosol compositionof claim 1 wherein said pharmaceutical is lidocaine.
 25. The aerosolcomposition of claim 1 wherein said pharmaceutical is bupivacaine. 26.The aerosol composition of claim 1 wherein said pharmaceutical isetidocaine.
 27. The aerosol composition of claim 1 wherein saidpharmaceutical is ropivacaine.
 28. The aerosol composition of claim 1wherein said pharmaceutical is benzocaine.
 29. The aerosol compositionof claim 1 wherein said pharmaceutical is phenylephrine.